Catalyst-Controlled Regiodivergent C-H Alkynylation of Thiophenes*.

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into (hetero)arenes, such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C-H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification. © 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Citation

Arup Mondal, Manuel van Gemmeren. Catalyst-Controlled Regiodivergent C-H Alkynylation of Thiophenes*. Angewandte Chemie (International ed. in English). 2021 Jan 11;60(2):742-746

PMID: 33044788

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